A strain of Drosophila (Uc) exhibiting very high rates of spontaneous mutation, chromosome rearrangement and sterility has been shown to contain up to 65 copies per diploid set of chromosomes of the retrovirus-like transposon gypsy. Reciprocal crosses of members of this strain to flies that contain no copies of gypsy in their euchromatic chromsomal segments, produce hybrid F1 females that show high rates of mutation associated with the mobilization and insertion of gypsy into chromosome sites previously free of the transposon. The hybrid females in turn produce offspring that are highly mutable. Examination of polytene chromosomes from F2 and F3 offspring of these crosses probed with 3H-labeled gypsy DNA in situ shows that gypsy is mobilized in somatic cells. This is consistent with the observation that most mutations transmitted through the germ lines appear as clusters. F1 males from reciprocal crosses of gypsy-free by gypsy-rich males individuals are completely stable mutationally and gypsy is not mobilized. Particular lines of Uc spontaneously become stable. In situ examination of these lines shows a great reduction in gypsy copy number (3 - 10) and no evidence of mobility of the transposon. Attempts to define the conditions responsible for the great increase in copy number and mobility of gypsy in the original Uc strain and among offspring of crosses involving that strain continue. Thus far we have shown that other systems of hybrid dysgenesis, P-M and I-R, play no role in the mobilization of the retrovirus-like transposon.